The specific aims of this proposal have not changed significantly from those outlined in the original application. They are now firmly based on demonstrated potent anti-HIV activity of polynucleotides which has previously been shown to be active against various non-HIV retroviruses. During the period of this project the following aims will be addressed: 1. Synthesize a series of nucleosides, nucleotides and polynucleotides of well-defined chemical structure. 2. Characterize the polynucleotides by enzymatic degradation, UV spectra, ultracentrifugation and, as appropriate, NMR; 3. Examine the physicochemical properties of the polymers by UV, circular dichroism, sedimentation and NMR; 4. Prepare sufficient quantities of monomers and polymers for evaluation by Southern Research Institute and by Dr. Thomas evans, University of Utah, as anti-AIDS agents; 5. Use the resulting biological data to develop structure-activity relationships (SAR and to correlate SAR with physicochemical properties; 6. Apply SAR to drive the synthetic program in the direction of optimal anti-AIDS agents.